Iron regulatory protein (IRP)-mediated iron homeostasis is critical for neutrophil development and differentiation in the bone marrow.
Iron regulatory protein (IRP)-mediated iron homeostasis is critical for neutrophil development and differentiation in the bone marrow.
复制标题
DOI：
10.1126/sciadv.abq4469
复制
发表时间：
2022-10-07
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
作者：
铁主要用于红细胞的血红蛋白化以输送氧气。然而，新出现的证据表明金属在造血过程中发挥着更广泛的作用，包括免疫系统的形成。哺乳动物细胞中铁的利用率由铁调节蛋白 1 (IRP1) 和 IRP2 控制。我们报告说，成年小鼠中 IRP1 和 IRP2 的整体破坏会损害骨髓中的中性粒细胞发育和分化，产生具有异常高糖酵解和自噬活性的未成熟中性粒细胞，导致中性粒细胞减少症。 IRP 通过确保细胞铁供应以及中性粒细胞生成的转录控制来促进分化为完全成熟的中性粒细胞，从而以细胞内在方式促进中性粒细胞分化。与中性粒细胞不同，单核细胞计数不受 IRP 和缺铁的影响，这表明铁对骨髓输出具有谱系特异性影响。这项研究揭示了 IRP 和铁代谢在先天免疫系统主要分支形成中的重要性，这一点此前未被认识到。维持造血细胞中的铁供应对于产生适当分化的中性粒细胞是必要的。
Iron is mostly devoted to the hemoglobinization of erythrocytes for oxygen transport. However, emerging evidence points to a broader role for the metal in hematopoiesis, including the formation of the immune system. Iron availability in mammalian cells is controlled by iron-regulatory protein 1 (IRP1) and IRP2. We report that global disruption of both IRP1 and IRP2 in adult mice impairs neutrophil development and differentiation in the bone marrow, yielding immature neutrophils with abnormally high glycolytic and autophagic activity, resulting in neutropenia. IRPs promote neutrophil differentiation in a cell intrinsic manner by securing cellular iron supply together with transcriptional control of neutropoiesis to facilitate differentiation to fully mature neutrophils. Unlike neutrophils, monocyte count was not affected by IRP and iron deficiency, suggesting a lineage-specific effect of iron on myeloid output. This study unveils the previously unrecognized importance of IRPs and iron metabolism in the formation of a major branch of the innate immune system. Maintenance of iron supply in hematopoietic cells is necessary for the production of properly differentiated neutrophils.
登录
查看更多内容
DOI：
10.1016/j.medj.2020.10.004
发表时间：
2021-02-12
期刊：
Med (New York, N.Y.)
影响因子：
--
作者：
Frost JN;Tan TK;Abbas M;Wideman SK;Bonadonna M;Stoffel NU;Wray K;Kronsteiner B;Smits G;Campagna DR;Duarte TL;Lopes JM;Shah A;Armitage AE;Arezes J;Lim PJ;Preston AE;Ahern D;Teh M;Naylor C;Salio M;Gileadi U;Andrews SC;Dunachie SJ;Zimmermann MB;van der Klis FRM;Cerundolo V;Bannard O;Draper SJ;Townsend ARM;Galy B;Fleming MD;Lewis MC;Drakesmith H
通讯作者：
Drakesmith H
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
4.6
作者：
Hameyer, Dorothe;Loonstra, Ate;Bockamp, Ernesto
通讯作者：
Bockamp, Ernesto
影响因子：
39.3
作者：
Haddad, Saba;Wang, Yong;Kempf, Tibor
通讯作者：
Kempf, Tibor
DOI：
10.1084/jem.20091488
发表时间：
2010-04-12
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Callens C;Coulon S;Naudin J;Radford-Weiss I;Boissel N;Raffoux E;Wang PH;Agarwal S;Tamouza H;Paubelle E;Asnafi V;Ribeil JA;Dessen P;Canioni D;Chandesris O;Rubio MT;Beaumont C;Benhamou M;Dombret H;Macintyre E;Monteiro RC;Moura IC;Hermine O
通讯作者：
Hermine O